Diisopropylethylamine → (s)-2-Chloro-5-fluoro-n-(1-(5-fluoropyridin-2-yl)ethyl)-6-morpholinopyrimidin-4-amine

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Reaction Conditions

Reaction Steps

A mixture of 4-(2,6-dichloro-5-fluoropyrimidin-4-yl)morpholine (Preparation 11a, 1.18 g, 4.68 mmol), (S)-1-(5-fluoropyridin-2-yl)ethanamine hydrochloride (prepared as described in WO2006/123113, 1.00 g, 4.69 mmol) and N,N′-diisopropylethylamine (3.27 mL, 18.77 mmol) in n-butanol (20 mL) was heated at 130° C. for two days. The solvent was evaporated under reduced pressure and the residue was purified by flash chromatography (0-5% ethyl acetate in hexanes to 5:94:1 ethyl acetate/hexanes/triethylamine) to give the title compound (0.700 g, 42%) as one major regioisomer. The chemical structures of both regioisomers were confirmed by NMR experiments (gHSQCAD and gHMBCAD).

Provenance & Evidence